Journal of Thoracic Oncology最新文献

英文中文

Advancing Lung Cancer Staging: Integrating IASLC Recommendations and Bioinformatics to Delineate Tumor Origins 推进肺癌分期：整合IASLC建议和生物信息学来描述肿瘤起源。

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.10.010

Michael Allgäuer PhD , Klaus Kluck MS , Petros Christopoulos MD , Markus Ball PhD , Anna-Lena Volckmar PhD , Teodora Radonic MD, PhD , Lukas Bubendorf MD , Paul Hofman MD, PhD , Claus Peter Heußel MD , Hauke Winter MD , Felix Herth MD , Michael Thomas MD , Bauke Ylstra PhD , Solange Peters MD, PhD , Peter Schirmacher MD , Daniel Kazdal PhD , Jan Budczies PhD , Albrecht Stenzinger MD , Martina Kirchner PhD

Introduction

Accurate distinction between separate primary lung carcinomas (SPLCs) and intrapulmonary metastases (IPMs) is essential for staging and treatment of multifocal NSCLC. Next-generation sequencing (NGS) enables assessment of clonal relatedness. The proposed International Association for the Study of Lung Cancer (IASLC) algorithm integrates histologic and molecular data, though its clinical utility is yet to be validated.

Methods

We focused on the molecular component of the algorithm and assessed 240 tumor pairs from 120 patients with formalin-fixed, paraffin-embedded tumor samples that underwent small-scale gene-panel NGS testing (31–54 genes) within routine clinical care. Most tumors were adenocarcinomas (n = 222), with 18 tumors other NSCLC subtypes. Inconclusive pairs by molecular classification were subjected to large-scale panel analyses (531 genes). In addition, we developed a bioinformatic method to complement and refine the IASLC method.

Results

In total, 22 tumor pairs (18%) remained inconclusive and 16 (13%) were classified ambiguous (probable SPLCs) using the molecular IASLC method. Resequencing classified nine of 22 inconclusive pairs as IPMs. Using a newly developed bioinformatic method for clonality classification incorporating likelihood ratios of mutational prevalence and small-scale sequencing, only three pairs remained inconclusive (2%). Tumors classified as SPLCs had a significantly longer overall survival than IPMs.

Conclusions

Small-scale panel sequencing of biopsy material allows unambiguous clonality determination in three of four cases. Large-scale sequencing resolves approximately half of inconclusive cases. Our bioinformatic method reduces inconclusive pairs to 2% even with small-scale NGS. It is made publicly available as a Shiny App. Clonality is reflected in survival data and therefore pivotal in daily clinical practice.

准确区分单独原发性肺癌（SPLCs）和肺内转移（IPMs）对于多灶性非小细胞肺癌（NSCLC）的分期和治疗至关重要。下一代测序（NGS）能够评估克隆亲缘性。提出的IASLC算法整合了组织学和分子数据，尽管其临床应用尚未得到验证。方法：我们专注于算法的分子组成部分，并评估了120例福尔马林固定石蜡包埋（FFPE）肿瘤样本中的240对肿瘤，这些肿瘤样本在常规临床护理中进行了小规模基因板NGS检测（31-54个基因）。大多数肿瘤为腺癌（222例），其余18例为非小细胞肺癌亚型。对531个基因的分子分类进行了大规模的面板分析。此外，我们开发了一种生物信息学方法来补充和完善IASLC方法。结果：使用分子IASLC方法，共有22对肿瘤（18%）仍未确定，16对（13%）被分类为模棱两可（可能的SPLCs）。重新测序将22对不确定对中的9对分类为IPMs。使用一种新开发的生物信息学方法进行克隆分类，结合突变流行率的似然比和小规模测序，只有3对仍不确定（2%）。归类为SPLCs的肿瘤的总生存期明显长于IPMs。结论：活检材料的小规模小组测序在4例中有3例可以明确地确定克隆性。大规模测序解决了大约一半的不确定病例。我们的生物信息学方法将不确定对减少到2%，即使是小规模的NGS。它作为一个闪亮的应用程序公开提供。克隆性反映在生存数据中，因此在日常临床实践中至关重要。

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引用次数: 0

Staging of Lung Cancer: A Call for Developing Uniform and Universal Key Performance Indicators and Benchmarks to Elevate Clinical Standards 肺癌分期：呼吁制定统一和通用的关键绩效指标和基准，以提高临床标准

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.11.007

Jan P. Van Meerbeeck MD, PhD , Jelle E. Bousema MD, PhD , Wen Wen MD , Paul E.Y. Van Schil MD, PhD

Accurate staging is pivotal in lung cancer management, yet standardized key performance indicators (KPIs) for staging practices are lacking. We identified a number of critical areas in the staging process and outlined a starter set of SMART KPIs for patients with early stage NSCLC. We propose clear definitions (numerators/denominators, timing anchors) and risk-adjusted benchmarks. These KPIs should be used to monitor and improve clinical practice; they are not intended to dictate the structure of the TNM classification, which must remain an objective, globally applicable anatomic language. Implementing staging KPIs can enhance diagnostic accuracy and treatment outcomes in lung cancer care.

准确的分期是肺癌管理的关键，但标准化的关键绩效指标（kpi）的分期实践缺乏。我们确定了分期过程中的一些关键领域，并为早期NSCLC患者概述了一套SMART kpi。我们提出了明确的定义（分子/分母，时间锚点）和风险调整基准。这些关键绩效指标应用于监测和改进临床实践；它们并不打算规定TNM分类的结构，TNM分类必须是一种客观的、全球适用的解剖学语言。实施分期kpi可以提高肺癌护理的诊断准确性和治疗效果。

引用次数: 0

Comment on COCOON: Daily 4% Chlorhexidine for Nail Care—Rationale, Safety, and Evidence Gaps 评论COCOON：每日4%氯己定用于指甲护理-原理，安全性和证据差距

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.10.011

Kei Kunimasa MD, PhD, Motohiro Tamiya MD, Shun Futamura MD, Kazumi Nishino MD, PhD

引用次数: 0

Brief Report: Critical Role for DNA-Based Sequencing in Discriminating Distinct Primary Lung Cancers With Different MET Exon 14 Skipping Mutations 简要报告：基于dna的测序在鉴别不同MET外显子14跳跃突变的原发性肺癌中的关键作用。

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.09.010

Federica Pecci MD , Prashasti Agrawal MD , Jessica S. Ross MD , Biagio Ricciuti MD, PhD , Seshiru Nakazawa MD, PhD , Alessandro Di Federico MD , Mihaela Aldea MD, PhD , Edoardo Garbo MD , Valentina Santo MD , Eleonora Gariazzo MD , Maisam Makarem MD, PhD , Danielle Haradon MS , Igor Odintsov MD , Marina Baine MD, PhD , William Travis MD , Soo-Ryum Yang MD , Paula A. Ugalde Figueroa MD , Katherine D. Gray MD , Mizuki Nishino MD, PhD , Maria Mayoral Penalva MD , Jamie E. Chaft MD

Introduction

MET exon 14 (METex14) skipping mutations are found in 3% to 4% of NSCLC and can be detected through DNA- or RNA-based sequencing assays. Although RNA sequencing simply reports skipping of exon 14, DNA sequencing assays indicate the precise DNA nucleotide changes that result in METex14 skipping. Here, we reveal the importance of DNA-based sequencing assays for identifying patients with multiple, distinct, METex14-mutant lung cancers.

Methods

NSCLC cases with available targeted exome next-generation sequencing through OncoPanel or Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assays were evaluated. Patients with METex14 mutations in ≥2 NSCLC tumor samples at any stage were reviewed to assess tumor relatedness based on clinicopathologic and genomic criteria.

Results

Among 589 patients with METex14-mutant NSCLC and available in-house next-generation sequencing, 112 had ≥2 NSCLC tumor samples sequenced with METex14 mutations; among these, seven patients had two distinct METex14-mutant primary lung cancers, and one patient had three primary METex14-mutant lung cancers. Four cases were synchronous primary cancers, occurring within 12 months of the initial diagnosis, whereas the other four were metachronous, occurring after 12 months. Comprehensive DNA genomic analysis confirmed the distinct clonality of the tumors, with each case showing different METex14 alterations and other distinct genomic events, supporting the diagnosis of independent primary lung cancers.

Conclusions

DNA-based sequencing of the MET gene improves staging accuracy to guide appropriate management for patients with multiple primary METex14-mutant NSCLCs.

背景：MET外显子14跳变（METex14）突变在3-4%的非小细胞肺癌（NSCLC）中发现，可以通过基于DNA和/或rna的测序分析检测。RNA测序仅仅报告了外显子14的跳跃，而DNA测序分析则精确地指出了导致MET外显子14跳跃的DNA核苷酸变化。在这里，我们证明了基于dna的测序检测对于识别多发性、不同的METex14突变肺癌患者的重要性。方法：通过oncoppanel或MSK-IMPACT检测评估具有靶向外显子组下一代测序（NGS）的NSCLC病例。根据临床病理和基因组标准，回顾≥2例NSCLC肿瘤样本中METex14突变的患者，以评估肿瘤相关性。结果：在589例METex14突变的非小细胞肺癌患者和现有的内部NGS中，112例有≥2例METex14突变的非小细胞肺癌肿瘤样本；其中7例患者有2种不同的METex14突变型原发性肺癌，1例患者有3种原发性METex14突变型肺癌。4例为同步原发性癌症，发生在初次诊断后12个月内，而另外4例为异时性癌症，发生在12个月之后。全面的DNA基因组分析证实了肿瘤的独特克隆性，每个病例显示不同的METex14改变以及其他独特的基因组事件，支持独立原发性肺癌的诊断。结论：基于dna的MET基因测序可提高分期准确性，指导多发原发性METex14突变非小细胞肺癌患者的适当治疗。

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引用次数: 0

Brief Report: Emphysema as a Prognostic Factor in Patients With Advanced NSCLC With COPD Receiving Immune Checkpoint Inhibitors 简要报告：肺气肿作为晚期非小细胞肺癌合并慢性阻塞性肺病患者接受免疫检查点抑制剂的预后因素。

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.10.007

Madeleine Di Frisco MD , Miguel F. Sanmamed MD , José María Ferrández MD , Anna Vilalta MD , Miguel Sogbe MD , Marta García-Goñi MD , Ángela Martin-Palmero MD , Samantha Aso-González MD , Ernest Nadal MD , Jaime Signes-Costa MD , Valentina Gambardella MD , Víctor Seguí Manzaneque MD , Paloma Martin MD , Amelia Insa MD , José Franco MD , Carmen Lores MD , Juan P. de Torres MD

Introduction

Chronic obstructive pulmonary disease (COPD) and emphysema are independent risk factors for lung cancer development and have been independently associated with longer overall survival (OS) in patients with NSCLC treated with immune checkpoint inhibitors (ICIs). However, their combined impact on prognosis remains unclear. This study evaluates emphysema as a prognostic factor in patients with COPD with advanced NSCLC (aNSCLC) undergoing immunotherapy.

Methods

This study included patients with aNSCLC with COPD (defined by spirometry) treated with single-agent ICI as first- or second-line treatment, from 2013 to 2024. Patients were classified based on visually detected emphysema on chest computed tomography.

Results

The study included 111 patients with COPD, of whom 77 had coexisting emphysema. Patients with COPD and emphysema had significantly longer OS compared with those without emphysema (17.3 versus 8.5 mo, p = 0.008), with a nonsignificant trend toward improved progression-free survival (3.3 versus 2.4 mo, p = 0.641). Emphysema remained an independent factor of better OS in multivariate analysis (hazard ratio: 0.49; 95% confidence interval: 0.30–0.81). Adverse event rates were similar regardless of emphysema status (p = 0.455).

Conclusions

This study suggests that visually detected emphysema on chest computed tomography could be a potential prognostic marker in patients with aNSCLC with COPD receiving ICIs. Further studies are guaranteed to confirm these findings.

背景：慢性阻塞性肺疾病（COPD）和肺气肿是肺癌发展的独立危险因素，并且在接受免疫检查点抑制剂（ICIs）治疗的非小细胞肺癌（NSCLC）患者中与更长的总生存期（OS）独立相关。然而，它们对预后的综合影响尚不清楚。本研究评估肺气肿作为COPD晚期非小细胞肺癌（aNSCLC）患者接受免疫治疗的预后因素。方法：本研究纳入2013年至2024年接受单药ICI作为一线或二线治疗的aNSCLC合并COPD（由肺活量测定定义）患者。根据胸部计算机断层扫描（cCT）目测肺气肿进行分类。结果：研究纳入111例COPD患者，其中77例合并肺气肿。COPD合并肺气肿患者的OS明显长于无肺气肿患者（17.3个月vs 8.5个月，p = 0.008）， PFS改善趋势不显著（3.3个月vs 2.4个月，p = 0.641）。在多因素分析中，肺气肿仍然是改善OS的独立因素（HR: 0.49; 95% CI: 0.30-0.81）。无论气肿状况如何，不良事件发生率相似（p = 0.455）。结论：本研究提示，cCT目测肺气肿可能是接受ICIs治疗的aNSCLC合并COPD患者的潜在预后指标。进一步的研究肯定会证实这些发现。

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引用次数: 0

A Grading System for Resected Invasive Squamous Cell Carcinoma of the Lung: A Multi-Institutional Study by the IASLC Pathology Committee 肺浸润性鳞状细胞癌的分级系统：IASLC病理委员会的一项多机构研究。

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.09.1761

Mari Mino-Kenudson MD , Sabina Berezowska MD , Yuko Minami MD, PhD , Shuyan Chen PhD , Meredith A. Ray PhD , Vilasinee Rerkpichaisuth MD , Mikiko Hashisako MD, PhD , Tereza Losmanova MD , Takuo Hayashi MD, PhD , Hyo-Sup Shim MD, PhD , Luisella Righi MD, PhD , Andréanne Gagné MD, PhD , Tae-Jung Kim MD, PhD , Lukas Bubendorf MD , Fernando Lopez-Rios MD, PhD , Daiske Matsubara MD, PhD , Jan von der Thüsen MD, PhD , Sylvie Lantuejoul MD, PhD , Anja C. Roden MD, PhD , Andrew Nicholson DM, FRCPath. , Mauro G. Papotti MD

Introduction

Tumor grading informs therapy and patient management across many organs, yet no consensus exists for grading invasive squamous cell carcinoma of the lung (LUSC). This study aimed to develop a globally applicable grading system using international cohorts.

Methods

Histologic features, including tumor budding, smallest tumor nest size, nuclear size, and tumor spread through air spaces (STAS), were evaluated in two training sets comprising 262 and 427 LUSCs resected without neoadjuvant therapy from three institutions. Kaplan-Meier and Cox proportional hazards models were used to identify features associated with recurrence-free survival (RFS) and overall survival (OS). Features significant in both training sets were used to construct a grading system, which was then validated in a test set (n = 827, five institutions). Interobserver agreement was assessed among 10 pathologists on 25 cases.

Results

Tumor budding (two-tier: cutoff at 10 buds per 0.785 mm²) was the only histologic feature significantly associated with both RFS and OS in multivariable analyses across both training sets. The proposed two-tier grading system—low-grade (0–9 buds), high-grade (≥10 buds)—was validated in the test set, demonstrating median RFS of 4.8 versus 1.6 years for low- versus high-grade tumors in the entire cohort and 7.2 versus 3.4 years within stage I patients. Interobserver agreement was moderate (Fleiss’ kappa = 0.524).

Conclusions

The authors propose a simple, prognostically relevant grading system for resected invasive LUSC based on tumor budding. It is reproducible across international data sets and practical for routine pathology, offering a unified framework for clinical and research use.

背景：肿瘤分级为许多器官的治疗和患者管理提供信息；但对于浸润性肺鳞状细胞癌（LUSC）的分级尚无共识。这项研究的目的是开发一个全球适用的分级系统使用国际队列。方法：组织学特征，包括肿瘤出芽、最小肿瘤巢大小、核大小和肿瘤通过空气间隙扩散（STAS），在两个训练集中进行评估，其中包括来自三家机构的262和427例未接受新辅助治疗的LUSCs。Kaplan-Meier和Cox比例风险模型用于识别与无复发生存期（RFS）和总生存期（OS）相关的特征。使用两个训练集中显著的特征来构建评分系统，然后在测试集中（n=827, 5个机构）进行验证。10名病理学家对25例病例进行了观察者间一致性评估。结果：在两个训练集的多变量分析中，肿瘤出芽（2层：每0.785 mm2切断10个芽）是唯一与RFS和OS显著相关的组织学特征。提出的两级分级系统-低级别（0-9个芽），高级别（bbb10个芽）-在测试集中得到验证，显示整个队列中低级别肿瘤和高级别肿瘤的中位RFS为4.8年和1.6年，I期患者的中位RFS为7.2年和3.4年。观察者间一致性为中等（Fleiss’kappa = 0.524）。结论：我们提出了一个简单的、与预后相关的基于肿瘤出芽的浸润性LUSC切除分级系统。它可在国际数据集中重现，并适用于常规病理学，为临床和研究使用提供了统一的框架。

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引用次数: 0

Corrigendum to “The International Association for the Study of Lung Cancer Staging Project: The Impact of Common Molecular Alterations on Overall Survival in NSCLC in Initial Analyses of the IASLC Ninth Edition Staging Database. [Journal of Thoracic Oncology Vol. 20 No. 10: 1423–1440]” 国际肺癌分期研究协会项目的勘误表：IASLC第九版分期数据库初步分析中常见分子改变对非小细胞肺癌总生存率的影响。《胸肿瘤学杂志》20卷10期：1423-1440。

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.10.006

David P. Carbone , Fred R. Hirsch , Raymond Uyiosa Osarogiagbon , Katherine K. Nishimura , Ming Sound Tsao , William D. Travis , Dawei Yang , Soo-Ryum Yang , Yasushi Yatabe , Luiz Henrique Araujo , Frank Detterbeck , Kendra J. Lechtenberg , Eric Lim , Philip C. Mack , José-María Matilla , Luis M. Montuenga , Andrew G. Nicholson , Kenichi Suda , Ricardo M. Terra , Ramón Rami-Porta , Murry W. Wynes

引用次数: 0

A Response to the Letter to the Editor: “Comment on COCOON: Daily 4% Chlorhexidine for Nail Care—Rationale, Safety, and Evidence Gaps” 致编辑信的回复：“对COCOON的评论：每日4%氯己定用于指甲护理-理由，安全性和证据差距”

IF 20.8 1区医学 Q1 ONCOLOGY

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Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.12.005

Byoung Chul Cho MD, PhD, Maxwell Sauder MD, Jairo Simoes MD, Nicolas Girard MD, PhD

引用次数: 0

Toward a Global Standard: Tumor Budding–Based Grading in Pulmonary Squamous Cell Carcinoma 迈向全球标准：基于肿瘤生长的肺鳞癌分级

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/j.jtho.2025.11.005

Emi Ibuki PhD, MD , Chihiro Yoshida PhD, MD , William D. Travis MD , Kyuichi Kadota PhD, MD

引用次数: 0

Board of Directors 董事会

IF 20.8 1区医学 Q1 ONCOLOGY

Journal of Thoracic Oncology

Pub Date : 2026-02-01 DOI: 10.1016/S1556-0864(25)03026-6

引用次数: 0

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